Three years ago we discovered a hepatitis virus in Beechey ground squirrels (GSHV) with ultrastructural, antigenic, molecular and biological properties similar to those of hepatitis B virus (HBV) of man and woodchuck hepatitis virus (WHV). In the past 3 years we have studied the host range of GSHV, its antigenic and polypeptide structure, its DNA structure and the viral DNA forms in infected liver. Little or no hepatitis and no hepatomas have been observed in chronically GSHV infected ground squirrels in contrast to moderately severe hepatitis and hepatomas frequently observed in WHV infected woodchucks and HBV infected humans. We propose to investigate the basis for the difference in incidence and severity of liver disease in the different virus-host systems. We will investigate the infectivity and pathogenicity of GSHV for woodchucks and WHV for ground squirrels to attempt to determine whether a difference in pathogenicity of the two virus, or a difference in response of the two hosts accounts for the observed difference in disease incidence. We will examine the viral DNA forms in GSHV infected ground squirrel liver and determine whether viral DNA becomes integrated in cellular DNA, and compare these findings with results in woodchuck and human systems. We will study the effects of environmental conditions and aflatoxin B1 on the pathogenic effects of GSHV in ground squirrels. We will study replication of GSHV DNA in infected liver and in tissue culture cells if they can be successfully infected. Finally, we will study the effect of antivirals on the high titer persistent infection seen in GSHV.